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Interleukin-11 (IL-11) has diverse biological effects in hematopoiesis has been shown to share important functions with IL-6. However, unlike IL-6, there has been little information about the expression of IL-11 in lymphoid malignancy. Using reverse transcriptase polymerase chain reaction, IL-11 transcript was found in a number of lymphoid cell lines. A high level of expression was found in follicular lymphoma cell line FL18, and this was also detectable by Northern blotting. When TPA/A23187 were added to the culture of bone marrow stromal cell line KM102, IL-11 transcripts were rapidly upregulated. In contrast, levels of IL-11 transcripts were not increased in FL18 even upon the stimulation. The addition of actinomycin D to the cultures showed that the half life of the transcripts was similar in both FL18 and KM102. This suggests that posttran scriptional processes might not be involved in the constitutive expression of FL18. The results of IL-11 bioassay and enzymed-linked immunosorbent assay showed that FL18 did not secrete biologically active IL-11 into the medium. IL-11 transcript was also found in lymphoma cells in patient with malignant lymphoma, but not in B and T lymphocytes from reactive hyperplasia. Our results indicate that IL-11 transcripts can sometimes be produced in the neoplastic transformation of lymphoid cells.

Surgical resection is the standard treatment for stage I non-small cell lung cancer (NSCLC). However, elderly patients with NSCLC often suffer from other conditions, such as chronic obstructive pulmonary disease (COPD) or cardiovascular disease, and are not suitable candidates for surgery. Different modalities to treat stage I NSCLC have been developed, such as stereotactic radiotherapy (SRT), proton beam radiotherapy and carbon ion radiotherapy (CIRT). Between April 1999 and November 2003, we treated 129 patients with stage I NSCLC using CIRT. In this study, we focused on 28 patients aged 80 years and older who underwent CIRT, and analyzed the effectiveness of CIRT in treating their lung cancer and the impact on their activity of daily life (ADL). The 5-year local control rate for these patients was 95.8%, and the 5-year overall survival rate was 30.7%, but there were no patients who started home oxygen therapy or had decreased ADL. Our data demonstrate that CIRT was effective in treating elderly patients with stage I NSCLC.

Background A phase I/II study was first conducted for the treatment of stage I non-small cell lung cancer (NSCLC) from 1994 to 1999 to determine the optimal dose. On the basis on the results, a phase II study using a regimen of four fractions during 1 week was performed. The purpose of the present study was to determine the local control and 5-year survival rates. Methods From December 2000 to November 2003, 79 patients with 80 primary lesions were treated. Using a fixed dose of 52.8 GyE for stage IA NSCLC and 60.0 GyE for stage IB NSCLC in four fractions during 1 week, the primary tumors were irradiated with carbon beams alone. The average age of the patients was 74.8 years. Sixty-two (78.5%) of these patients were medically inoperable. Local control and survival were determined using the Kaplan-Meier method. The data were statistically processed using the log-rank test. Results All patients were observed for a minimum of 3 years or until death, with a median follow-up time of 38.6 months, ranging from 2.5 to 72.2 months. The local control rate for all patients was 90% (T1: 98%, T2: 80%). The patients' 5-year lung cancer-specific survival rate was 68% (IA: 87%, IB: 42%). The overall survival was 45% (IA: 62%, IB: 25%). Half of the deaths were attributable to intercurrent diseases. No toxic reactions in the lung greater than grade 3 were detected. Conclusion Carbon ion beam radiotherapy with a regimen of four fractions during 1 week has been proven as a valid alternative to surgery for stage I NSCLC and to offer particular benefits, especially for elderly and inoperable patients.

Purpose: A phase I/II study on carbon ion radiotherapy for Stage I non–small-cell lung cancer (NSCLC) was first conducted between 1994 and 1999 and determined the optimal dose. Second, a Phase II study using the optimal dose was performed. The purpose of the present study was to clarify the local control and 5-year survival rates. Methods and Materials: Between April 1999 and December 2000, 50 patients with 51 primary lesions were treated. Using a fixed dose of 72 GyE in nine fractions over 3 weeks, the primary tumors were irradiated with carbon ion beams alone. The average age of the patients was 74.5 years. Thirty-three (66%) of these were medically inoperable. Local control and survival were determined by using the Kaplan-Meier method and the data were statistically processed by using the log–rank test. Results: All patients were observed for a minimum of 5 years or until death with a median follow-up time of 59.2 months (range, 6.0–83.0 months). The local control rate for all patients was 94.7%. The patients’ 5-year cause-specific survival rate was 75.7% (IA: 89.4; IB: 55.1), and overall survival 50.0% (IA: 55.2; IB: 42.9). No toxic reactions in the lung greater than Grade 3 were detected. Conclusions: Carbon ion radiotherapy, a new treatment modality with superior benefits in terms of quality of life and activity of daily living, has been proven as a valid alternative to surgery for Stage I NSCLC and to offer particular benefits, especially for elderly and inoperable patients.

Purpose: To evaluate the toxicity and efficacy of carbon ion radiotherapy (CIRT) for locally advanced cervical cancer by two phase I/II clinical trials. Methods and Materials: Between June 1995 and January 2000, 44 patients were treated with CIRT. Thirty patients had stage IIIB disease and 14 patients had stage IVA disease. Median tumor size was 6.5 cm (4.2-11.0 cm). The treatment consisted of 16 fractions of whole pelvic irradiation and 8 fractions of local boost. In the first study, the total dose ranged from 52.8 to 72.0 gray equivalent (GyE) (2.2 to 3.0 GyE/fraction). In the second study, the whole pelvic dose was fixed at 44.8 GyE, and an additional 24.0 or 28.0 GyE was given to the cervical tumor (total dose: 68.8 or 72.8 GyE). Results: No patient developed severe acute toxicity. In contrast, 8 patients developed major late gastrointestinal complications. The doses resulting in major complications were over 60 GyE. All patients with major complications were surgically salvaged. The 5-year local control rates for patients in the first and second studies were 45% and 79%, respectively. When treated with 62.4 GyE or more, the local control was favorable even for the patients with stage IVA disease (69%) or for those with tumors > 6.0 cm (64%). Conclusions: In CIRT for advanced cervical cancer, the dose to the intestines should be limited to less than 60 GyE to avoid major complications. Although the number of patients was small, the results supported the continued investigation to confirm therapeutic efficacy.

Summary Background and purpose: Carbon ion beams provide physical and biological advantages over photons. This study summarizes the experiences of carbon ion radiotherapy at the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences Materials and Methods: Between June 1994 and August 2003, a total of 1,601 patients with various types of malignant tumors were enrolled in phase I/II dose-escalation studies and clinical phase II studies. All but malignant glioma patients received carbon ion radiotherapy alone with a fraction number and overall treatment time being fixed for each tumor site, given to one field per day and 3 or 4 days per week. In dose-escalation studies, the total dose was escalated by 5 or 10 % increments to ensure a safe patient treatment and to determine appropriate dose levels. Results: In the initial dose-escalation studies, severe late complications of the recto-sigmoid colon and esophagus were observed in those patients who received high dose levels for prostate, uterine cervix and esophageal cancer. Such adverse effects, however, did shortly disappear as a result of determining safe dose levels and because of improvements in the irradiation method. Carbon ion radiotherapy has shown improvement of outcome for tumor entities: a) locally advanced head and neck tumors, in particular those with non-squamous cell histology including adenocarcinoma, adenoid cystic carcinoma, and malignant melanoma; b) early stage NSCLC and locally advanced NSCLC; c) locally advanced bone and soft tissue sarcomas not suited for surgical resection; d) locally advanced hepatocellular carcinomas; e) locally advanced prostate carcinomas, in particular for high-risk patients; f) chordoma and chondrosarcoma of the skull base and cervical spine, and g) post-operative pelvic recurrence of rectal cancer. Treatment of malignant gliomas, pancreatic, uterine cervix, and esophageal cancer is being investigated within dose-escalation studies. There is a rationale for the use of short-course RT regimen due to the superior dose localization and the unique biological properties of high-LET beams. This has been proven in treatment of NSCLC and hepatoma, where the fraction number has been successfully reduced to 4∼12 fractions delivered within 1∼3 weeks. Even for other types of tumors including prostate cancer, bone/soft tissue sarcoma and head/neck tumors, it was equally possible to apply the therapy in much shorter treatment times as compared to conventional RT regimen. Conclusion: Carbon ion radiotherapy, due to its physical and biologic advantages over photons, has provided improved outcome in terms of minimized toxicity and high local control rates for locally advanced tumors and pathologically non-squamous cell type of tumors. Using carbon ion radiotherapy, hypofractionated radiotherapy with application of larger doses per fraction and a reduction of overall treatment times as compared to conventional radiotherapy was enabled.

CD30, a member of the TNF/NGF receptor superfamily, is firstly thought to be a specific marker for Hodgkin's and Reed-Sternberg's cells. Recent studies revealed that its function is not restricted to a tumor marker of Hodgkin and Reed-Sternberg's cells. It might play an important role in the immune system and the cascade which would lead to the apoptotic phenomenon. Nowadays, the expression of CD30 is thought to have relation to various diseases, not only Hodgkin's disease and anaplastic large cell lymphoma (ALCL), but also atopic diseases and AIDS. This comes from the fact that CD30 expression has correlate to the Th2 cytokine production.The pathway of CD30/CD30L signal is now being revealed, which involves the TNF receptor associated factor (TRAF)-1, TRAF-2, TRAF-3, similar to other member of this family. However, the exact role of CD30 and its regulatory mechanism for the expression is not clear yet. In this review we summarized the latest information of CD30.

A new autopsy imaging (AI) system was introduced at the Research Center Hospital for Charged Particle Therapy (RCCPT) in January 2000. Autopsy imaging is a postmortem and preautopsy diagnostic procedure using magnetic resonance imaging (MRI). Scanning is performed with a 1.5 Tesla MRI system before autopsy. The AI results are reported to the pathologist and, in light of this information, autopsy is performed with minute precision. Autopsy imaging was performed on 37 cancer cases. In seven cases, AI was less informative than the autopsy, but in 30 cases, more precise reports on the final diagnosis were available with the combined application of autopsy and AI than autopsy alone, particularly in eight limited autopsy cases. Thus, AI provides critical and supplementary information for autopsy; furthermore, AI itself is a unique imaging system of great importance.

Purpose To evaluate the toxicity and antitumor effect of carbon ion radiotherapy for hepatocellular carcinoma within a Phase I-II trial. Methods and materials Between June 1995 and February 1997, 24 patients with histopathologically proven hepatocellular carcinoma were treated to 15 fractions within 5 weeks in a step-wise dose-escalation study. The disease stage was Stage II in 10, IIIA in 6, and IVA in 8 patients. The Common Toxicity Criteria, Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer criteria, and Child-Pugh score were used to evaluate toxicity. The antitumor effect was evaluated by the tumor response, cumulative local control, and survival rates. Results During a median follow-up of 71 months (range, 63–83 months), no severe adverse effects and no treatment-related deaths occurred. The Child-Pugh score did not increase by >2 points after the start of therapy. In 78% and 75% of all patients, the score did not increase by >1 point in the early and late phase, respectively. The overall tumor response rate was 71%. The local control and overall survival rate was 92% and 92%, 81% and 50%, and 81% and 25% at 1, 3, and 5 years, respectively. Conclusion Carbon ion radiotherapy appears safe and effective for patients with hepatocellular carcinoma. Additional clinical studies using a larger subject group are required to confirm the therapeutic efficacy.

The National Institute of Radiological Sciences in Chiba, Japan (NIRS) has the highest number of patients with lung cancer treated with carbon ion beams in the world. This report describes the techniques and clinical trials that have been undertaken at NIRS and preliminary results of a current study on single-fraction irradiation. The data are compared to recent results for the treatment of peripheral stage I lung cancer from the literature.